Allyl thiophenes



Patented Oct. '11, 1949 ALLYL 'rmornnnns I Philip D.

Caesar. Wenonah, and Darwin E.

Badertscher, Woodbury, N. J., assignors to 80- cony-Vacuum Oil Company, Incorporated, a

corporation of New York No Drawing. Application August 10, 1946, Serial No. 589,817

12 Claims.

, 1 This invention relates to a method for producing alkyl thiophenes having an unsaturated side chain and, more articularly, is directed to a process involving the condensation of a thiophene with an alcohol containing an oleflnic linkage between two carbon atoms of aliphatic character, one of which is linked directly by a single bond to the carbinol carbon atom. V

The condensation of a thiophene with such alcohols has heretofore not been accomplished. The usual methods of introducing a side chain on the thiophene ring, such as through the Grlgnard reaction or the Friedel-Crafts synthesis, have not been satisfactory when unsaturated alcohols are employed as alkylating agents. Thus, in the preparation of allyl thiophene, by reacting Z-thienyl magnesium iodide with allyl bromide, the cost of the reagents involved has been prohibitive in so far as commercial utilization of this method is concerned. The Friedel- Crafts synthesis, which heretofore has been employed to some extent in the preparation of thiophene derivatives, cannot be used with any degree of success with unsaturated alcohols, inherently characterized by the presence of a double bond and a hydroxyl group. The presence of an olefinic linkage between two carbon atoms, one of whichis adjacent to a carbinol carbon atom, appears to be highly susceptible in the presence of a Friedel-Crafts catalyst to addition reactions. It has heretofore been postulated that a Friedel- Crafts catalyst, such as aluminum chloride, promotes the addition of intermediate products to the olefinic linkage of unsaturated alcohols when these are employed as alkylating agents, thereby greatly reducing or eliminating entirely the production of the desired alkyl compound having an unsaturated side chain. The soundness of this postulation need not be explored here, except to note that the prior art has recognized that the Friedel-Crafts reaction is not applicable with any degreeof success when an unsaturated alcohol is employed as one of the reactants.

It has now been discovered that the condensation of a thiophene and an alcohol containing an oleflnic linkage between two carbon atoms of aliphatic character, one of which is linked directly by a single bond to the carbinol carbon atom, can be efiected in an eflicient manner by reacting thiophene or thiophene derivatives with such alcohol in the presence of controlled amounts of sulfuric acid as a catalyst. It has been found that by using sulfuric acid as a catalyst, the above-mentioned difficulties encountered in the preparation of alkyl compounds having unsaturated side chains have largely been overcome. Thus, by employing controlled amounts of sulfuric acid as a catalyst, the addition of mtermedlate products to the olefinic linkage of the unsaturated alcohol employed has been largely eliminated and a commercially attractive yield of the desired alkylated thiophene is obtained as product. The introduction of unsaturated alkyl side chains to the thiophene ring using a sulfuric acid catalyst, moreover, affords a convenient and inexpensive method of synthesizing these compounds in comparison to the relatively complicated and expensive Grignard reaction heretofore employed.

It is accordingly an object of the present invention to provide an eflicient process for synthesizing alkyl thiophenes having an unsaturated side chain. Another object is to provide a process for catalytically carrying out the condensation of thiophene or a thiophene derivative with an unsaturated aliphatic alcohol. A still further object is to afford a process for catalytically alkylating thiophene with an unsaturated alcohol in a relatively simple and direct manner which can be readily carried out using an inexpensive, easily obtainable catalyst. A'very important object is to provide a process capable of reacting thiophene or its derivatives with an unsaturated aliphatic alcohol without an accompanying addition reaction taking place at the olefinic linkages of said alcohol.

These and other objects which will be recognized by those skilled in the art are attained in accordance with the present invention, wherein thiophene or its derivatives are condensed in the presence of sulfuric acid as a catalyst with an alcohol containing an olefinic linkage between two aliphatic carbon atoms, one of which is linked directly by a single bond to the carbinol carbon atom. Although it has been suggested that thiophene is similar to benzene in some respects, it is of interest to note that condensation of benzene and an unsaturated alcohol of the type described is not promoted to any extent by sulfuric acid of concentrations contemplated for use in the process of the present invention.

Sulfuric acid in concentrations ranging from about 50 per cent to about 98 per cent has been found to be an efiective catalyst for promoting the condensation of thiophene and an unsaturated alcohol to yieldan alkyl thiophene having an unsaturated side chain. However, under the preferred reaction conditions discussed below, a sulfuric acid concentration ofgreater than about "I per cent is necessary 3 in order to obtain a sub.- stantial yield of the desired alkylated product. The reaction of thiophene with unsaturated alcohols of the type described above is thus dependent on the concentration and also on the amount of sulfuric acid employed. This condition is believed due, at least in part, to the diluent action of water formed during the condensation reaction. As such water is formed. the acid becomes diluted and consequently loses its activity so that at a concentration below about 50 per cent, the acid is no longer eflective as acatalyst. Even at concentrations of the order of 50 per cent, rather drastic conditions of temperature and amounts of sulfuric acid are necessary in order to effect the condensation reaction.

The unsaturated alcohols to be used herein as alkylating agents are those characterized by the presence of an olefinic linkage between two aliphatic carbon atoms, one of which is linked directly to the carbinol carbon atom. Thus, the alcohols contemplated for use in the process of this invention have the general structural formula: I

million where R1. Ra. Ra. R4 represent either hydrogen atoms or saturated alkyl radicals, said radicals generally containing not more than above five carbon atoms. Representative alcohols which may be employed accordingly include allyl alcohol, 3 butene-2-ol, 2 butene-l-ol, 3 pentene-2-ol, 1 pentene-3-ol, 2 pentene-l-ol, 2 hexene-l-ol, 3 hexene-2-ol, etc. These alcohols are given merely by way of examples and are not to be construed as limiting, since other similar unsaturated alcohols which will readily suggest themselves to those skilled in the art may likewise be used.

, Thiophene or derivatives of thiophene having one or more substituent groups, such as halogen, alkyl, or aryl groups attached to the thiophene ring, may be condensed with an alcohol of the above type in accordance with this invention. The 2- and 5- positions in the thiophene ring, being adjacent to the sulfur atom. are generally much more reactive than the 3- and 4- positions and in the condensation reaction, the entering unsaturatedalkyl group will preferably attach itself to the carbon atom adjacent to the sulfur. When the 2- position of the thiophene ring is already occupied by a substituent group or atom, the entering group will preferably attach itself to the 5- position. When the 3- position is occupied, the unsaturated alkyl substituent will enter for the most part at the 2- position. However, in some instances, a small portion of the 3, 5 product may be'obtained.

The condensation of thiophene or its derivatives with an unsaturated alcohol of the type described can be carried out employing equimolar quantities of thiophene and alcohol. However, the presence of an excess of thiophene has been foundgenerally to be desirable, givingan increased yield of the desired product. The reaction rate of the condensation is dependent on the temperature at which the process is carried out, increasing with increasing temperatures. Ingeneral, temperatures of from about 0 C. to about 80 C. may be employed at atmospheric pressure. More elevated temperatures up to about 200 C. or higher may be. used when the I reaction is carried out under pressure. Generally,

amazes however, the use of too high a temperature is to be avoided since it has been found that with the more concentrated sulfuric acid solutions, i. e., above about 75 per cent, excessive resiniflcation of the thiophene is encountered. However, with the more dilute acids down to about 50 per cent concentration, the use of temperatures in the range of 80 C. to 200 C. are necessary if any condensation is to take place. The preferable temperature range, as will be shown hereinafter, is between about 40 C. and about 60 C.

The effect of increased pressure, theoretically,

' is toward increased reaction but froma practical standpoint, this is not a very great effect with reactions such as those involved herein which go readily at normal pressures. The temperature to be employed will depend on the amount and concentration of the sulfuric acid catalyst employed, on the time of reaction, and On the nature of the alcohol reactant used. Ordinarily, a pressure suflicient to maintain the reactants in the liquid phase is employed and this is more or less dependent upon the temperature. As a general rule, the higher the temperature, the higher the pressure and the lower the reaction time needed to effect the condensation. It is, of course, to be understood that the reaction variables of amount and concentration of sulfuric acid used, temperature, time, and pressure are more or less interdependent.

Under the conditions encountered in the process of this invention, the reaction period will generaly lie between about and about 10 hours. Under the preferred reaction conditions hereinafter set forth, however, it has been found that the condensation reaction is substantially complete in about 1 hour. The sulfuric acid catalyst preferably employed herein, of concentration between about 75 and about 98 per cent, may be present in amounts as small as 0.2 mole per mole of alcohol used. The upper limit as to catalyst amount will be dependent upon the temperature employed and the concentrationt of acid. However, amounts of sulfuric acid in excess of about i 2 moles per mole of alcohol will generally contribute little to the process of this invention and,

as pointed 'out above, excessive amounts of concentrated sulfuric acid may cause resinification of the thiophene reactant, particularly at the higher temperatures. With the preferred sulfuric acid concentration of between about 75 and 98 per cent, an amount of acid between about 0.2 and about 0.8 mole per mole of alcohol was found to yield optimum results.

The following detailed examples are for the purpose of illustrating modes of effecting the condensation of thiophene with allyl alcohol in accordance with the process of this invention.

It is to be clearly understood, however, that the invention is not to be limited to the specific alcohol disclosed or to the manipulations and conditions set forth in the example mammal To a mixture of 84 grams of thiophene (1 mole) and 30 grams of allyl alcohol (0.5 mole) maintained at a temperature in the range of from 78 C. to 85 C., were slowly added, over a period ture were separated and the latter layer was washed with dilute potassium hydroxide solution until neutral and then distilled. About 8 grams of allyl thiophene, having a boiling point of 160-165" C., were obtained. This represents a organic layer was then washed with dilute alkali solution until substantially neutral and then dis yield of about 18 per cen of y, as d on tilled. Of the 77 grams of product distilled, 65 the amount of thiophene consumed. grams of unreacted benzene were recovered. EXAMPLE 2 Only two grams of a material boiling between 120 C..and 180 C. were obtained. The remain- O a mixture 0f 34 grams of tmophene (1 mole) der was a resinous tar. This example thus indiand 30 grams of allyl alcohol (050111016) f cates that the condensation of benzene with allyl tained at a temperature O m 30 W 40 alcohol, in the presence of sulfuric acid, isnegwere slowly added, over a period of 25 minutes, 1igib1e 42 grams (0.42 mole) of 96 per cent sulfuric acid. Further examples Showing the condensation o The total f eactlon Perlod 2 hours, at the end thiophene and allyl alcohol, and using sulfuric Of which tune the pl'oduct mlxhlre cooled to acid concentrations of '75 and 85 per cent, were room temperature. The resulting acid and carried out in the manner set forth in the preganlc layers were separated. The organic layer ceding examples and are tabulated below: was then washed with dilute alkali solution until substantially neutral and then distilled. Ap- TABLE I proximately 44 grams of thiophene were recovered. Twenty grams of allyl thiophene, boiling Alkylatwn thiophene alcohol in the range of ISO-165 C., were obtained. This yzed by 75% H250 quantity represents a yield of 34 per cent, based on the weight of thiophene consumed. About Example 5 6 7 8 9 22 grams of a high boiling liquid residue remained after distillation of the allyl thiophene. p g m (1 7H5 50-50 .35 was 75.85

R D t' ,h 1. 2.0 .0 EXAMP LE 3 ciffiwi'ivfiafsom 2 6 6 Weight, gins. s4 s4 42 21 10 To a mixture of 84 grams of thiophene (1 mole) Moles 0. 05 0.05 0.33 0.10 08 and grams of allyl alcohol (0.5 mole), main- 30 flggggm g f 45 25 15 tained at a temperature of from C. to 50 0., ei t. e s 84 84 84 84 84 were slowly added, over a period of 30 minutes, t 2131mgr" L0 L0 42 grams (0.42 mole) of 96 per cent sulfuric acid. geisha ems... 30 30 s0 s0 30 The total reaction was 1 hour, at the end of which zfj 'irg 5g g" 5 5 5 5 5 time the product mixture was cooled to room tem- 5 grgs 50 00 09 perature. The resulting acid and organic layers ,;%5$,,; n, 11 12 m 7 About 1 were separated. The organic layer was then RL %l 31 22 32 washed with dilute alkali solution until substan- 5 5 5,3; tially neutral and then distilled. Approximately P119119 consumed) 27 21 29 32 44 grams of thiophene were recovered. Twenty- 40 TABLE II Alkylation of thiophene with allyl alcohol catalyzed by 85% H2804 Example 10 11 12 13 14 15 16 Temperature, C 40 40 40 40 60 70-80 Run Duration, hr 1.0 1.0 2.0 ...0 2.0 2.0 1.0 Catalyst (85% H180 Weight, glnS s4 s4 s4 00 42 42 42 Moles 0.71 0.11 0.11 0.52 0. a5 0. s5 0 Addition Time, min 45 45 00 25 21 Thiophene Charged:

Weight, gIIlS s4 s4 s4 s4 s4 84 M01 1.0 1.0 1.0 1.0 1.0 1.0 1 Ally] Alcohol Charged Weight, gmS 30 30 s0 s0 s0 30 Moles 0.5 0.5 0.5 0.5 0.5 1 0.5 0 Recovered Thiophene, gms 33 44 42 57 50 55 Products, gms.:

Allyl Thiophene a 23 22 s 25 23 Liquid Residue 52 25 21 14 23 22 Yield of Allyl Thiophene (percent Theor. based on thiophene consumed) ll 39 36 45 50 53 32 seven grams of allyl thiophene, boiling in the range of ISO-165 C., were obtained. This quantity represents a yield of 46 per cent, based on the weight of thiophene consumed. About 24 grams of a high boiling liquid residue remained after distillation of the allyl thiophene.

EXAlVfPLE 4 It is to be noted from Example 9 in Table I,

in which only 0.16 mole of sulfuric acid per mole of alcohol was employed, that little allyl thiophene was obtained, indicating that this amount is insufficient to promote effectively the condensation reaction. I

With the higher concentration acid of per cent in Table II, it is seen, in comparing the figures for Examples 10 and 1 that the reaction temperature has an appreciable efiect on the yield of desired product. Thus, the temperature with the higher concentrated acids appears to have a greater'efiect on the reaction than with the lower concentrated acid. For example, the yield figures for Examples 5 and 6, in which '15 per cent cases as ea sulfuric acid was used, do not differ appreciably. A comparison of Examples 11 and 12, in which the only variable is the duration of the run, shows that practically identical results were obtained. This would indicate that the reaction was substantially complete-in about 1 hour's time and that the additional hour of reaction period used in Example 12 contributed little to the final result. A comparison of Examples 12-14 shows that as the amount of acid is reduced from about 1.4 moles per mole of alcoholto about 0.7 mole per mole of alcohol, the yield of allyl thiophene is increased. Thus, it may be concluded that with an 85 per cent sulfuric acid catalyst under the reaction conditions set forth in Table II, the amount of acid should be maintained below about 0.7 mole per mole of alkylating agent in. order to obtain the optimum yield of desired alkylated thiophene. A comparison of Examples 15 and 16 again indicates that the temperature is an important reaction condition to be considered in effecting a maximum yield of allyl thiophene. It is seen from those two examples that an approximate 20-degree increase in temperature causes the yield of product to decrease by about 20 per cent.

The foregoing examples accordingly show that the condensation of thiophene and allyl alcohol is effectively catalyzed by the presence of Sulfuric acid to yield allyl thiophene. It will be undertsood by those skilled in the art that the numerous reaction variables lying within the preferable ranges set forth herein are interdependent and the conditions of reaction stipulated for the present process are not to be unduly limited except as hereinafter defined by the appended claims.

We claim:

1. A process for condensing thiophene with an alcohol containing an olefinic linkage between two carbon atoms of aliphatic character, one of which is linked directly by a single bond to the carbinol carbon atom, comprising contacting said reactants in the presence of at least about 0.2 mole of sulfuric acid, of from about 50 per cent to about 98 per cent concentration, per mole of said alcohol.

2. A process for condensing thiophene with an alcohol containing an olefinic linkage between two carbon atoms of aliphatic character, one of which is linked directly by a single bond to the carbinol carbon atom, comprising contacting said reactants in the presence of at least about 0.2 mole of sulfuric acid, of from about 75 per cent to about 98 per cent concentration, per mole of said alcohol.

3. A process for condensing thiophene with an alcohol containing an olefinic linkage between two carbon atoms of aliphatic character, one of which is linked directly by a single bond to the carbinol carbon atom, comprising contacting said reactants at a temperature between about 0 and about 200 C.in the presence of at least about 0.2 mole of sulfuric acid, of from about 50 per cent to about 98 per cent concentration, per mole of said. alcohol.

4. A process for condensing thiophene with an alcohol containing an olefinic linkage between two carbon atoms of aliphatic character, one of which is linked directly by a single bond to the carbinol carbon atom, comprising contacting said reactants at a temperature between about 0 and about 80 C. in the presence of at least about 0.2

mole of sulfuric acid, of from about 50 per cent to about 98 per cent concentration, per mole of said alcohol.

5. A process for condensing thiophene with an alcohol containingan olefinic linkage between two carbon atoms of aliphatic character, one of which is linked directly by a single bond to the carbinol carbon atom, comprising contacting said reactants at a temperature between about 40 C. and about 60 C. in the presence of at least about 0.2 mole of sulfuric acid, of from about per cent to about 98 per cent concentration, per mole of said alcohol. 7

6. A process for condensing thiophene with an alcohol containing an olefinic linkage between two carbon atoms of aliphatic character, one of which is linked directly by a single bond to the carbinol carbon atom, comprising contacting said reactants in the presence of between about 0.2 mole and about 0.8 mole of sulfuric acid, of from about 75 per cent to about 98 per cent concentration, per mole of said alcohol.

7. A process for condensing thiophene with allyl alcohol, comprising contacting said reactants in the presence of at least about 0.2 mole of sulfuric acid, of from about 50 per cent to about 98 per cent concentration, per mole of said alcohol.

8. A process for condensing thiophene with allyl alcohol, comprising contacting said reactants in the presence of at least about 0.2 mole of sulfuric acid, of from about 75 per cent to about 98 per cent concentration, per mole of said alcohol.

9. A process for condensing thiophene with allyl alcohol, comprising contacting said reactants at a temperature between about 0 and about 200 C. in the presence of at least about 0.2 mole of sulfuric acid, of from about 50 per cent to about 98 per cent concentration per mole of said alcohol.

10. A process for condensing thiophene with allyl alcohol, comprising contacting said reactants at a temperature between about 0 and about C. in'the presence of at least about 0.2

. of said alcohol.

12. A process for condensing thiophene with allyl alcohol, comprising contacting said reactants in the presence of between about 0.2 mole and about 0.8 mole of sulfuric acid, of from about 75 per cent to about 98 per cent concentration, per mole of said alcoho PHILIP D. CAESAR. DARWIN E. BADERTSCHER.

REFERENCES oI'rEn The following references are of record in the file of this patent:

J. Am. Chem. Soc. 61, .1521-2 (1939).

Richter, Organic Chemistry, p. 649-550, John Wiley, 1938. 1 

